Abstract

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The metabolic profile of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI)

Presented by Kiat Ruxrungtham, Thailand.

Ruxrungtham K.¹, Bellos N.², Morales-Ramirez J.³, Timerman A.⁴, Madruga J.⁵, Katabira E.⁶, Vanveggel S.⁷, Peeters M.⁷, Stevens M.⁷, Williams P.⁷, Woodfall B.⁷, Boven K.⁸

¹Thai Red Cross AIDS Research Centre, Bangkok, Thailand, ²Southwest Infectious Disease Associates, Dallas, TX, United States, ³Clinical Research, San Juan, Puerto Rico, ⁴Hospital Heliopolis, São Paulo, Brazil, ⁵Centro de Referência e Treinamento DST-AIDS, São Paulo, Brazil, ⁶Makerere University, Kampala, Uganda, ⁷Tibotec BVBA, Mechelen, Belgium, ⁸Tibotec Inc., Yardley, PA, United States

Objectives: TMC278 is a next-generation NNRTI with potent and sustained efficacy in ARV-naïve patients. The metabolic profile (lipids, glucose and insulin sensitivity) of TMC278 was assessed and compared to efavirenz (EFV).
Methods: TMC278-C204 is an ongoing randomized, active controlled, partially blinded dose-finding study to evaluate the efficacy, safety and tolerability of three doses of TMC278 (25mg, 75mg, 150mg q.d.) in ARV-naïve HIV-1 infected patients. The active control is EFV 600mg q.d.; all treatments include 2 NRTIs. Changes in fasting lipids, insulin and glucose were measured over a 48-week treatment period and HOMA-IR was calculated.
Results: 279 patients were randomized to TMC278 and 89 to EFV; AZT/3TC was used by 76% of patients and TDF/FTC by 24%. 33% were female and the median age was 35 years. There were no substantial differences for metabolic parameters between the different TMC278 dose groups.

Mean change from baseline in parameter (± SD)	All TMC278 combined n = 279	EFV n = 89	p-value EFV vs TMC278
TC (mg/dL)	5 (± 30)	31 (± 30)	<0.001
LDL-C (mg/dL)	1 (± 25)	15 (± 23)	<0.001
HDL-C (mg/dL)	5 (± 9)	12 (± 10)	<0.001
Ratio TC/HDL-C	- 0.45 (± 0.99)	- 0.30 (± 0.85)	0.47
TG (mg/dL)	-10 (± 79)	18 (± 66)	0.001
Glucose (mg/dL)	1.4 (± 12.0)	3.0 (± 13.7)	0.029
Log (HOMA-IR)	0.2 (± 0.7)	0.1 (± 0.7)	0.51

For the combined TMC278 group the mean changes from baseline in TC, LDL-C and TG were statistically significantly lower than for EFV. The change in HDL-C was statistically significantly higher for EFV than for TMC278 and the ratio of TC/HDL-C was not significantly different.
Conclusions: Higher TC, LDL-C and TG were observed with EFV than with TMC278. There were minimal changes from baseline in glucose and insulin sensitivity, which were not significantly different between TMC278 and EFV.

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The metabolic profile of TMC278, an investigational NNRTI

Disclaimer: This additional information has been submitted by the abstract author after the abstract has been accepted for the conference and has not been reviewed by the conference organizers.

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